Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04481256
Other study ID # 73750
Secondary ID
Status Recruiting
Phase N/A
First received
Last updated
Start date November 11, 2020
Est. completion date June 1, 2023

Study information

Verified date December 2022
Source Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Contact Linde Veen
Phone 020-5665955
Email l.veen1@amsterdamumc.nl
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The primary objective of this study is to assess the feasibility of treatment with bintrafusp alfa combined with definitive chemoradiation (carboplatin, paclitaxel and radiation) in patients with squamous cell carcinoma of the esophagus or gastroesophageal junction.


Description:

Non-randomized feasibility study with paclitaxel, carboplatin, bintrafusp alfa, and radiation. Paclitaxel 50 mg/m2 and carboplatin AUC = 2 will be given intravenously (i.v.) on days 1, 8, 15, 22, 29 and 36. Bintrafusp alfa will be given i.v. every three weeks on day 1, 22, and 43 at a dose of 2400 mg. External beam radiotherapy will be delivered to a total dose of 50.4 Gy in 28 fractions of 1.8 Gy, 5 fractions per week, starting the first day of the first cycle of chemotherapy.


Other known NCT identifiers
  • NCT04595149

Recruitment information / eligibility

Status Recruiting
Enrollment 49
Est. completion date June 1, 2023
Est. primary completion date June 1, 2023
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - Histologically proven squamous cell carcinoma of the esophagus or gastro esophageal junction. - Surgically irresectable (T1-T4a, N0 or N+, M0), as determined by Endoscopic Ultra Sound (EUS), PET scan and diagnostic CT scan of neck, thorax and abdomen. Patients with M1 disease solely on the basis of supraclavicular metastasis are eligible. Patients with resectable tumors refusing radical surgery are eligible. - Locoregional recurrences without distant metastasis after surgery alone or endoscopical resection - Locoregional recurrences without distant metastasis after neoadjuvant chemoradiation + resection or definitive chemoradiation outside the previously irradiated area, provided that full dose of radiation can safely be delivered. - Tumors that cannot be passed with an endoscope for endoscopic ultrasound are eligible if all other criteria are fulfilled. - If the tumor extends below the gastroesophageal (GE) junction into the proximal stomach, the bulk of the tumor must involve the esophagus or GE junction. - Age = 18. - ECOG performance status 0-2 (cf. Appendix A). - Adequate hematological, renal and hepatic functions defined as: - Neutrophils = 1.5 x 109/L - Platelets = 100 x 109/L - Hemoglobin = 5.6 mmol - Total bilirubin = 1.5 x upper normal limit - ASAT and ALAT = 1.5 x upper normal limit, Alkaline Phosphatase = 2.5 x upper normal limit. - PT (INR) = 1.5 x upper normal limit and aPTT = 1.5 x upper normal limit. - Creatinine clearance (Cockroft) > 60 ml/min - Written, voluntary informed consent - Patients must be accessible to management and follow-up in the treatment center Exclusion Criteria: - Past or current history of malignancy other than entry diagnosis interfering with prognosis of esophageal cancer. - Patient with tracheo-esophageal fistula or extension into the mucosal layer of the trachea, highly at risk to develop fistula. Thus, tumor extension to the trachea is allowed, but not through the trachea. - Patients with pathological lymph nodes at both supraclavicular and truncus coeliacus level. - Pregnancy (positive serum pregnancy test), planning to become pregnant, and lactation. - Patient (male or female) in the reproductive age is not willing to use highly effective methods of contraception (per institutional standard) during treatment and for 6 months (male or female) after the end of treatment. - Previous chemotherapy, radiation and/or treatment with checkpoint inhibitors for the currently present esophageal tumor. - Previous chemotherapy and/or treatment with targeted agents and/or checkpoint inhibitors for other forms of cancer within the last six months. - Previous radiation to the mediastinum precluding full dose radiation of the currently present esophageal tumor. - Persisting grade >1 NCI CTCAE 5.0 toxicity (except alopecia and vitiligo) related to prior therapy; however, grade =2 sensory neuropathy is acceptable. - Presence of an esophageal stent. - History of bleeding diathesis or major bleeding event (grade = 2) in the month prior to first dose of trial treatment. - Clinically significant cardiovascular disease precluding safe treatment with chemoradiation. - Evidence of pulmonary fibrosis and/or clinically significant impairment of lung function precluding safe treatment with chemoradiation. In case of doubt about pulmonary function, a lung function test should be performed and, in case of abnormalities, discussed with the principle investigator. - Serious underlying medical condition which would impair the ability of the patient to receive the planned treatment, including prior allergic reactions to drugs containing cremophor, such as teniposide or cyclosporine. - Mental status that would prohibit the understanding and giving of informed consent. - Inadequate caloric- and/or fluid intake despite consultation of a dietician and/or tube feeding. - Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine for patients with a history of autoimmune-related hypothyroidism, insulin for patients with type 1 diabetes mellitus, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Patients with vitiligo with dermatological manifestations only are eligible to enter the study. - A diagnosis of immunodeficiency or is receiving systemic steroid therapy (>10 mg/day prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. - Diagnosis of HIV unless stable on antiretroviral therapy for at least 4 weeks, no evidence of multi-drug resistance, viral load of < 400 copies/ml and CD4+ T-cells = 350 cells/µl. - Active HBV/HCV. Participants on a stable dose of antiviral therapy with HBV/HCV viral load below the limit of quantification are eligible. - Evidence of interstitial lung disease or active, non-infectious pneumonitis. - An active infection requiring systemic therapy, which has not resolved 3 days (simple infection such as cystitis) to 7 days (severe infection such as pyelonephritis) prior to the first dose of trial treatment. - Administration of a live vaccine within 30 days prior to the first dose of trial treatment. Seasonal flu vaccines that do not contain a live virus are permitted. - Patients with prior allogeneic stem cell or solid organ transplantation.

Study Design


Related Conditions & MeSH terms


Intervention

Radiation:
External beam radiotherapy
External beam radiotherapy will be delivered to a total dose of 50.4 Gy in 28 fractions of 1.8 Gy, 5 fractions per week, starting the first day of the first cycle of chemotherapy
Drug:
Bintrafusp alfa
Bintrafusp alfa will be given i.v. every three weeks on day 1, 22, and 43 at a dose of 2400 mg.
Paclitaxel
Paclitaxel 50 mg/m2 will be given intravenously (i.v.) on days 1, 8, 15, 22, 29 and 36.
Carboplatin
Carboplatin AUC = 2 will be given intravenously (i.v.) on days 1, 8, 15, 22, 29 and 36.

Locations

Country Name City State
Netherlands Academic Medical Center, Medical Oncology Amsterdam

Sponsors (18)

Lead Sponsor Collaborator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) Catharina Ziekenhuis Eindhoven, Deventer Ziekenhuis, Elisabeth-TweeSteden Ziekenhuis, Erasmus Medical Center, Isala, Leiden University Medical Center, Maastro Clinic, The Netherlands, Medisch Centrum Leeuwarden, Radiotherapeutic Institute Friesland, Radiotherapy Group Deventer, Rijnstate Hospital, The Netherlands Cancer Institute, UMC Utrecht, University Medical Center Groningen, Verbeeten Insituut Tilburg, ZGT, Zuyderland Medisch Centrum

Country where clinical trial is conducted

Netherlands, 

Outcome

Type Measure Description Time frame Safety issue
Other Biomarker To perform exploratory biomarker analyses for treatment response 54 months
Primary Feasibility difined as the percentage of patients completing at least two cycles of bintrafusp alfa The primary outcome of this study is the percentage of patients that completes at least two cycles of bintrafusp alfa together with their chemoradiotherapy regimen. 36 months
Secondary Incidence and severity of toxicity Incidence and severity of toxicity defined according to CTCAE v5 and and Radiation Oncology Group (RTOG) criteria. 36 months
Secondary Percentage completion Percentage completion of chemotherapy and radiation treatment 36 months
Secondary Percentage withdrawal rate Percentage withdrawal rate from chemoradiation due to bintrafusp alfa related complications 36 months
Secondary locoregional progression Infield locoregional progression free survival 36 months
Secondary progression Any progression free survival 36 months
Secondary Survival Overall survival 36 months
Secondary Quality of life (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ C30)) Overall Quality of life ranging from 0-100 with 100 being best Quality of Life with special focus on dysphagia 36 months
Secondary adverse events To determine the number and grade of adverse events of bintrafusp alfa combined with chemoradiotherapy according to NCI common toxicity criteria (CTC) version 5 36 months
See also
  Status Clinical Trial Phase
Recruiting NCT02743832 - A Study on Tumor Budding Guiding Individualized Surgical Planning of Early-stage Oral Squamous Cell Carcinoma. N/A
Active, not recruiting NCT02229656 - Olaparib and Radiotherapy in Head and Neck Cancer Phase 1
Completed NCT00389727 - Simultaneous Integrated Boost (SIB)- IMRT Phase 2
Recruiting NCT02328391 - STUDY OBSERVATIONAL OF ERLOTINIB AS SECOND LINE TREATMENT IN PATIENTS WITH SQUAMOUS NSCLC AND EGFR NATIVE N/A
Completed NCT00875381 - Analysis of Melanocytes (Pigment Cells) in Sun-Exposed Skin N/A
Completed NCT00534950 - Randomized Multicenter Study of 5 vs 6 Weekly Fraction of RT in the Treatment of SCC of the Head and Neck N/A
Terminated NCT00073450 - Study of Lonafarnib in Patients With Recurrent Squamous Cell Carcinoma of the Head and Neck (Study P02530) Phase 2
Terminated NCT01441128 - -02341066 and PF-00299804 for Advanced Non-Small Cell Lung Cancer Phase 1
Recruiting NCT05970497 - A Study Assessing KB707 for the Treatment of Locally Advanced or Metastatic Solid Tumors Phase 1
Completed NCT01362127 - Neoadjuvant Chemotherapy Versus Radiochemotherapy for Cancer of the Esophagus or Cardia Phase 2
Completed NCT00240682 - Study of Cetuximab in Squamous Cell Carcinoma of the Skin Expressing EGFR Phase 2
Terminated NCT02254044 - Dose Escalation of Bivatuzumab Mertansine in Patients With Advanced Squamous Cell Carcinoma of the Head and Neck or Esophagus Phase 1
Active, not recruiting NCT00829192 - Phase II AK Study in Organ Transplant Patients Phase 2
Completed NCT00539630 - TAX + Cisplatin + 5 F/U vs Cisplatin + 5 F/U in SCCHN Phase 3
Completed NCT00313027 - Cervical Nodal Mets in Squamous Cell Carcinoma of H&N - MRI, FDG-PET, & Histopathologic Correlation N/A
Recruiting NCT04564989 - Prospective Observational Study to Validate Circulating HPVDNA and Prognostic Genomic Biomarkers in HPV-associated OPSCC
Not yet recruiting NCT06094829 - Tobacco and Alcohol Influence on Oncogenic Drivers and Somatic Evolution in the Oral Mucosa
Active, not recruiting NCT02664935 - National Lung Matrix Trial: Multi-drug Phase II Trial in Non-Small Cell Lung Cancer Phase 2
Terminated NCT02438995 - Super-Selective Intraarterial Infusion of Cetuximab (Erbitux) With or Without Radiation Therapy for the Treatment of Unresectable Recurrent Squamous Cell Carcinoma of the Head and Neck Phase 1
Terminated NCT00673049 - Trial Of CP-751, 871 And Erlotinib In Refractory Lung Cancer Phase 3